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Moleculebiological analysis of HLA class II in autoimmune hepatitis.

自身免疫性肝炎HLA II类的分子生物学分析。

基本信息

批准号：
03454227
负责人：
KIYOSAWA Kendo
金额：
$ 4.03万
依托单位：
Shinshu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

项目摘要

1. To investigate the association between autoimmune hepatitis and HLA alleles in Japanese patients, serological typing and class II genotyping were performed using the polymerase chain reaction-restriction fragment length polymorphisms(PCR-RFLP)method. Serologicaltyping showed that HLA-B54, -Dr53, and -DQ4 were significantly associated with autoimmune hepatitis (88.7%). In PCR-RFLP typing, the frequency of Dw between the patients and thecontrols who were DR4-positive. The significant increase observed in DQA1**0301 and DQB1**0401 was explained by a linkage disequilibrium with DR4. Six DR4-negative patients had DR2, but there was no significant difference in the frequency of the DR2-positive controls. No DQB1 allele was significantly associated with autoimmune hepatitis. These findings suggest that the basic amino acid at position 13, which is present only on the DR4 B1 molecules (Arg on DR2 and His on DR4), contributes to the susceptibility to autoimmune hepatitis among the Japanese.2 … More . We clarified the clinical and immunogenetical differences between patients with autoimmune hepatitis (AI-CAH), and patients with type C chronic active hepatitis(C-CAH) and type B chronic active hepatitis (B-CAH) who were positive for autoantibodies and hyperglobulinemia. While histories of blood transfusion, intravenous drug abuse and tattoo were seen frequently in patients with type C-CAH, they were rare in patients with AI-CAH.The severe subjective symptoms including anorexia, lethargy, icterus, high fever and extrahepatic manifestations, and severe abnormality of biochemical data were seen in AI-CAH.HLA-DR4 was the most frequently associated with AI-CAH(89%) and 6 DR4-negative patients were positive for DR2. HLA-DNA typing showed that there was no significant difference in the frequency of DR4-associated Dw-alleles between the patients and controls who were positive for DR4. These findings suggest that the basic amino acid at position 13, which is present only DR2 and DR4-B1 molecules, may contribute to the susceptibility to autoimmune hepatitis of Japanese. Thus, we conclude that AI-CAH is a genetically restricted disease and different from C-CAH which is a viral infectious disease. Less

1.为了研究日本患者自身免疫性肝炎与HLA等位基因之间的相关性，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法进行血清学分型和II类基因分型。血清学分型结果显示，HLA-B54、-Dr 53和-DQ 4与自身免疫性肝炎显著相关（88.7%）。在PCR-RFLP分型中，DR 4阳性者与对照者之间Dw的频率差异有统计学意义（P < 0. 05）。在DQA 1 **0301和DQB 1 **0401中观察到的显著增加由与DR 4的连锁不平衡解释。6名DR 4阴性患者有DR 2，但DR 2阳性对照的频率无显著差异。DQB 1等位基因与自身免疫性肝炎无显著相关性。这些发现表明，仅存在于DR 4 B1分子上的13位碱性氨基酸（DR 2上的Arg和DR 4上的His）导致了日本人对自身免疫性肝炎的易感性。 ...更多信息 .我们阐明了自身免疫性肝炎（AI-CAH）患者与自身抗体和高球蛋白血症阳性的C型慢性活动性肝炎（C-CAH）和B型慢性活动性肝炎（B-CAH）患者之间的临床和免疫遗传学差异。C-CAH患者输血史、静脉吸毒史、纹身史多见，AI-CAH患者较少见，自觉症状严重，主要表现为厌食、嗜睡、黄疸、高热、肝外表现等。AI-CAH的HLA-DR 4与AI-CAH的相关性最高（89%），DR 4 - 6与AI-CAH的相关性最高（80%），阴性患者DR 2阳性。HLA-DNA分型结果显示，DR 4阳性的患者与对照组之间DR 4相关Dw等位基因频率无显著差异。这些结果表明，在位置13的碱性氨基酸，这是目前只有DR 2和DR 4-B1分子，可能有助于对自身免疫性肝炎的易感性，日本。因此，我们认为AI-CAH是一种遗传限制性疾病，与C-CAH不同，C-CAH是一种病毒感染性疾病。少